Identification of crucial genes associated with rat traumatic spinal cord injury

Yang,Zibin; Lv,Qiao; Wang,Zhengxiang; Dong,Xiliang; Yang,Rongxin; Zhao,Wei

doi:10.3892/mmr.2017.6267

Identification of crucial genes associated with rat traumatic spinal cord injury

Authors:
- Zibin Yang
- Qiao Lv
- Zhengxiang Wang
- Xiliang Dong
- Rongxin Yang
- Wei Zhao
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Affiliations: Department of Spinal Surgery, The People's Hospital of Dali Prefecture, Dali, Yunnan 671000, P.R. China
Published online on: March 1, 2017 https://doi.org/10.3892/mmr.2017.6267
Pages: 1997-2006
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the key genes associated with traumatic spinal cord injuries (TSCI). The dataset GSE52763 was downloaded from the Gene Expression Omnibus, for which lumbar spinal cord samples were obtained from rats at 1 and 3 weeks following contusive spinal cord injury and 1 week subsequent to a sham laminectomy, and used to identify differentially expressed genes (DEGs). Functional enrichment analysis, co‑expression analysis and transcription factor (TF) identification were performed for DEGs common to the 1 and 3 week injury samples. In total, 234 upregulated and 51 downregulated DEGs were common to the 1 and 3 week injury samples. The upregulated DEGs were significantly enriched in Gene Ontology terms concerning immunity (e.g. Itgal and Ccl2) and certain pathways, including natural killer cell mediated cytotoxicity [e.g. Ras‑related C3 botulinum toxin substrate 2 (Rac2) and TYRO protein tyrosine kinase binding protein (Tyrobp)]. The downregulated DEGs were highly enriched in female gonad development [e.g. progesterone receptor (Pgr)], and the steroid biosynthesis pathway. A total of 139 genes had co‑expression associations and the majority of them were upregulated genes. The upregulated co‑expressed genes were predominantly enriched in biological regulation, including TGFB induced factor homeobox 1 (Tgif1) and Rac2. The downregulated co‑expressed genes were enriched in anatomical structure development (e.g. Dnm3). A total of 92 co‑expressed genes composed the protein‑protein interaction network. Additionally, 9 TFs (e.g. Pgr and Tgif1) were identified from the DEGs. It was hypothesized that the genes including Tgif1, Rac2, Tyrobp, and Pgr may be closely associated with TSCI.

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1	Jain NB, Ayers GD, Peterson EN, Harris MB, Morse L, O'Connor KC and Garshick E: Traumatic spinal cord injury in the United States, 1993–2012. Jama. 313:2236–2243. 2015. View Article : Google Scholar : PubMed/NCBI
2	Chen MJ, Kress B, Han X, Moll K, Peng W, Ji RR and Nedergaard M: Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia. 60:1660–1670. 2012. View Article : Google Scholar : PubMed/NCBI
3	Chen M, Ni Y, Liu Y, Xia X, Cao J, Wang C, Mao X, Zhang W, Chen C, Chen X and Wang Y: Spatiotemporal expression of EAPP modulates neuronal apoptosis and reactive astrogliosis after spinal cord injury. J Cell Biochem. 116:1381–1390. 2015. View Article : Google Scholar : PubMed/NCBI
4	Zhu P, Hata R, Nakata K, Cao F, Samukawa K, Fujita H and Sakanaka M: Intravenous infusion of ginsenoside Rb1 ameliorates compressive spinal cord injury through upregulation of Bcl-xL and VEGF. Int J Neurol Neurother. 2:12015. View Article : Google Scholar : PubMed/NCBI
5	De Biase A, Knoblach SM, Di Giovanni S, Fan C, Molon A, Hoffman EP and Faden AI: Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity. Physiol Genom. 22:368–381. 2005. View Article : Google Scholar
6	Byrnes KR, Garay J, Di Giovanni S, De Biase A, Knoblach SM, Hoffman EP, Movsesyan V and Faden AI: Expression of two temporally distinct microglia-related gene clusters after spinal cord injury. Glia. 53:420–433. 2006. View Article : Google Scholar : PubMed/NCBI
7	Sharp J, Frame J, Siegenthaler M, Nistor G and Keirstead HS: Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells. 28:152–163. 2010.PubMed/NCBI
8	Shin HY, Kim H, Kwon MJ, Hwang DH, Lee K and Kim BG: Molecular and cellular changes in the lumbar spinal cord following thoracic injury: Regulation by treadmill locomotor training. PLoS One. 9:e882152014. View Article : Google Scholar : PubMed/NCBI
9	Gautier L, Cope L, Bolstad BM and Irizarry RA: Affy-analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
10	Smyth GK: Limma: Linear models for microarray dataBioinformatics and computational biology solutions using R and Bioconductor. Springer; pp. 397–420. 2005, View Article : Google Scholar
11	Obayashi T and Kinoshita K: Rank of correlation coefficient as a comparable measure for biological significance of gene coexpression. DNA Res. 16:249–260. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kohl M, Wiese S and Warscheid B: Cytoscape: Software for visualization and analysis of biological networksData Mining in Proteomics. Springer; pp. 291–303. 2011
13	Maere S, Heymans K and Kuiper M: BiNGO: A Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 21:3448–3449. 2005. View Article : Google Scholar : PubMed/NCBI
14	Zhang HM, Liu T, Liu CJ, Song S, Zhang X, Liu W, Jia H, Xue Y and Guo AY: Animal TFDB 2.0: A resource for expression, prediction and functional study of animal transcription factors. Nucleic Acids Res. 43(Database Issue): D76–D81. 2015. View Article : Google Scholar : PubMed/NCBI
15	Yang Y, Hwang CK, D'Souza UM, Lee SH, Junn E and Mouradian MM: Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription. J Biol Chem. 275:20734–20741. 2000. View Article : Google Scholar : PubMed/NCBI
16	Huang J, Wah IY, Pooh RK and Choy KW: Molecular genetics in fetal neurology. Semin Fetal Neonatal Med. 17:341–346. 2012. View Article : Google Scholar : PubMed/NCBI
17	Kerr TC, Cuykendall TN, Luettjohann LC and Houston DW: Maternal Tgif1 regulates nodal gene expression in Xenopus. Dev Dyn. 237:2862–2873. 2008. View Article : Google Scholar : PubMed/NCBI
18	Sha L, Kitchen R, Porteous D, Blackwood D, Muir W and Pickard B: SOX11 target genes: Implications for neurogenesis and neuropsychiatric illness. Acta Neuropsychiatrica. 24:16–25. 2012. View Article : Google Scholar : PubMed/NCBI
19	Ramsey SA, Klemm SL, Zak DE, Kennedy KA, Thorsson V, Li B, Gilchrist M, Gold ES, Johnson CD, Litvak V, et al: Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics. PLoS Comput Biol. 21:e10000212008. View Article : Google Scholar
20	Didsbury J, Weber RF, Bokoch GM, Evans T and Snyderman R: Rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem. 264:16378–16382. 1989.PubMed/NCBI
21	Iversen PO, Hjeltnes N, Holm B, Flatebo T, Strom-Gundersen I, Ronning W, Stanghelle J and Benestad HB: Depressed immunity and impaired proliferation of hematopoietic progenitor cells in patients with complete spinal cord injury. Blood. 96:2081–2083. 2000.PubMed/NCBI
22	Numano F, Inoue A, Enomoto M, Shinomiya K, Okawa A and Okabe S: Critical involvement of Rho GTPase activity in the efficient transplantation of neural stem cells into the injured spinal cord. Mol Brain. 2:372009. View Article : Google Scholar : PubMed/NCBI
23	Tian Y and Autieri MV: Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells: A role for Rac2 in VSMC activation. Am J Physiol Cell Physiol. 292:C841–C849. 2007. View Article : Google Scholar : PubMed/NCBI
24	Hall A and Lalli G: Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol. 2:a0018182010. View Article : Google Scholar : PubMed/NCBI
25	Lanier LL, Corliss BC, Wu J, Leong C and Phillips JH: Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 391:703–707. 1998. View Article : Google Scholar : PubMed/NCBI
26	Gingras MC, Lapillonne H and Margolin JF: TREM-1, MDL-1 and DAP12 expression is associated with a mature stage of myeloid development. Mol Immunol. 38:817–824. 2002. View Article : Google Scholar : PubMed/NCBI
27	Jones KJ: Gonadal steroids as promoting factors in axonal regeneration. Brain Res Bull. 30:491–498. 1993. View Article : Google Scholar : PubMed/NCBI
28	Pakulski C: Neuroprotective properties of sex hormones. Anestezjol Intens Ter. 43:113–118. 2011.(In Polish). PubMed/NCBI
29	Gonzalez SL, Labombarda F, González Deniselle MC, Guennoun R, Schumacher M and De Nicola AF: Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord. Neuroscience. 125:605–614. 2004. View Article : Google Scholar : PubMed/NCBI